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In an animated sequence, a plane flying through the fictional Bukuvu region in the heart of Africa crashes. A child onboard the plane disappears into the jungle, eventually growing up to be George.

Ursula Stanhope, a San Francisco heiress, tours Uganda with local guide Kwame and a trio of porters Kip, N'Dugo, and Baleto. Ursula is joined by her fiancé, Lyle Van De Groot, who tracked her down with help from two poachers Max and Thor. Lyle intends on whisking Ursula home to marry her, but his pompous buffoonery irritates the porters, particularly when he nearly kills one by shaking a rope bridge. Kwame tells Ursula of the legend of the "White Ape", said to be a superhuman primate who rules the local jungle.

The next day, Lyle tries to drag Ursula away but they are attacked by a lion. Lyle tries to flee but knocks himself out. Ursula is rescued by the legendary White Ape, revealed to be George, who is child-like and has a habit of crashing into trees when swinging on vines.

George takes Ursula to his treehouse home, where she meets his extensive family of apes, including an intelligent talking gorilla named Ape. George also has an African elephant named Shep who he treats like a dog, a toco toucan named Tookie who provides gossip, and Little Monkey, an emotional capuchin monkey. Meanwhile, Lyle, Max, Thor, and the porters search for Ursula. George befriends Ursula, teaching her how to swing on vines, and tries to woo her following Ape's advice to do so in the manner that a gorilla would. When this fails, he then charms her with a dance around a campfire.

Lyle, Max, and Thor discover George's treehouse, and Lyle accidentally shoots George with a firearm he mistook for a novelty lighter. While Lyle is arrested, Ursula flies George back to San Francisco to get him medical treatment. George explores the city and rescues a paraglider on the Bay Bridge. Ursula, uninterested in marrying Lyle, admits the truth to her parents, but her overbearing mother Beatrice objects, wanting her to marry the wealthy Lyle. At a party, Beatrice takes George aside and tells him to give up Ursula for her own sake or else she would turn George into a eunuch. In Africa, Max and Thor capture Ape with the intention of using him to make money. Tookie is sent to retrieve George, and they return to rescue Ape. Ursula realizes she loves George and departs to follow him with her father Arthur's blessing.

Ape tricks the poachers into circling the jungle and returning to the treehouse where George confronts them. Ursula and George's animal family aid him in defeating the poachers. However, Lyle appears, having escaped jail, joined a cult, and is now a wedding minister, intending on forcing Ursula into marriage and has George captured by mercenaries. George escapes with help from his ape friends, and pursues Ursula and Lyle down river rapids, successfully rescuing Ursula by performing the "biggest swing in jungle history". Lyle enters a dark cave, believing Ursula is still in the life raft, and ends up wedding a female gorilla. After professing their love to each other, George and Ursula wed in Africa, later have a son named George Jr, who they present to the animals from atop Pride Rock.

In a post-credits scene, Ape reveals he has become a famous entertainer in Las Vegas, using Max and Thor as stunt men.

In the opening animated sequence, various animals swing on vines with young George, his "dog" Shep (actually an elephant), fetches a crocodile instead of a log, and a wildebeest falls in love with a bushman wearing a wildebeest mask.

In the live action film, a whole host of animals are seen. George fights with a lion, accidentally swings on a snake instead of a vine, rides an elephant, talks to a bird, and lives with various monkeys and apes.

The lion, elephant, and bird scenes were all filmed with a mix of real animals, puppetry (especially for the lion fight), and CGI (to show the elephant acting like a dog). The scenes with the orangutan, a chimpanzee, and the capuchin monkeys were filmed with live animals, but some computer work was used in a scene wherein the little monkey imitates George.

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Review aggregator Rotten Tomatoes gave the film a score of 56% based on 52 reviews with an average rating of 5.3/10. The consensus states: "George of the Jungle is faithful to its source material—which, unfortunately, makes it a less-than-compelling feature film". Roger Ebert awarded the movie three out of four stars, praising the film as "good-natured" and complimenting the cast's comedic performances.[4]